Department of Physiology, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Pharmacology-Toxicology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Physiology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Eur J Prev Cardiol. 2016 Jan;23(1):33-40. doi: 10.1177/2047487314558377. Epub 2014 Nov 11.
Reperfusion is mandatory after ischaemia, but it also triggers ischaemia-reperfusion (IR)-injury. It is currently unknown whether heart failure alters the magnitude of IR-injury. Ischaemic preconditioning can limit IR-injury. Since ischaemic preconditioning is typically applied in subjects at risk for cardiovascular complications, it is of clinical importance to understand its efficacy in heart failure patients.
To examine the magnitude of endothelial IR-injury, and the ability of ischaemic preconditioning to protect against endothelial IR-injury in heart failure.
We included 15 subjects with heart failure (67 ± 10 years, New York Heart Association class II/III) and 15 healthy, age- and sex-matched controls (65 ± 9 years). We examined brachial artery endothelial function using flow-mediated dilation before and after arm IR (induced by 5-min ischaemic handgrip exercise +15 min reperfusion). IR was preceded by ischaemic preconditioning (consisting in three cycles of 5-min upper arm cuff inflation to 220 mmHg) or no inflation.
A significant interaction-effect was found for the change in flow-mediated dilation after IR between groups (two-way ANOVA interaction-effect: p = 0.01). Whilst post-hoc analysis revealed a significantly decline in flow-mediated dilation in both groups (p < 0.05), the decline in flow-mediated dilation in heart failure patients (6.2 ± 3.6% to 3.3 ± 1.8%) was significantly larger than that observed in controls (4.9 ± 2.1 to 4.1 ± 2.0). Neither in heart failure patients nor controls was the decrease in flow-mediated dilation after IR altered by ischaemic preconditioning (three-way ANOVA interaction: p = 0.87).
We found that patients with heart failure are associated with exaggerated endothelial IR-injury compared with age- and sex-matched, healthy controls, which may contribute to the poor clinical prognosis in heart failure. Furthermore, we found no protective effect of ischaemic preconditioning (3 × 5-min forearm ischaemia) against endothelial IR-injury in heart failure patients.
缺血后必须再灌注，但再灌注也会引发缺血再灌注（IR）损伤。目前尚不清楚心力衰竭是否会改变 IR 损伤的程度。缺血预处理可以限制 IR 损伤。由于缺血预处理通常应用于有心血管并发症风险的患者，因此了解其在心力衰竭患者中的疗效具有重要的临床意义。
研究心力衰竭患者内皮细胞 IR 损伤的程度，以及缺血预处理防止内皮细胞 IR 损伤的能力。
我们纳入了 15 例心力衰竭患者（67±10 岁，纽约心脏协会 II/III 级）和 15 例年龄和性别匹配的健康对照者（65±9 岁）。我们在手臂 IR 前后使用血流介导的扩张来检测肱动脉内皮功能（IR 通过 5 分钟缺血性手握运动+15 分钟再灌注来诱导）。IR 之前进行缺血预处理（包括三个 5 分钟的上臂袖带充气至 220mmHg 的循环）或不充气。
组间 IR 后血流介导的扩张变化存在显著的交互效应（双因素方差分析交互效应：p=0.01）。虽然事后分析显示两组的血流介导的扩张都显著下降（p<0.05），但心力衰竭患者的血流介导的扩张下降（6.2±3.6%至 3.3±1.8%）明显大于对照组（4.9±2.1%至 4.1±2.0%）。在心力衰竭患者和对照组中，IR 后血流介导的扩张的减少都不受缺血预处理的影响（三因素方差分析交互：p=0.87）。
我们发现心力衰竭患者与年龄和性别匹配的健康对照组相比，内皮细胞 IR 损伤更为严重，这可能导致心力衰竭的临床预后不良。此外，我们发现缺血预处理（3×5 分钟前臂缺血）对心力衰竭患者内皮细胞 IR 损伤没有保护作用。
